Host Gut Motility Promotes Competitive Exclusion within a Model Intestinal Microbiota

Abstract

The gut microbiota is a complex consortium of microorganisms with the ability to influence important aspects of host health and development. Harnessing this “microbial organ” for biomedical applications requires clarifying the degree to which host and bacterial factors act alone or in combination to govern the stability of specific lineages. To address this issue, we combined bacteriological manipulation and light sheet fluorescence microscopy to monitor the dynamics of a defined two-species microbiota within a vertebrate gut. We observed that the interplay between each population and the gut environment produces distinct spatiotemporal patterns. As a consequence, one species dominates while the other experiences sudden drops in abundance that are well fit by a stochastic mathematical model. Modeling revealed that direct bacterial competition could only partially explain the observed phenomena, suggesting that a host factor is also important in shaping the community. We hypothesized the host determinant to be gut motility, and tested this mechanism by measuring colonization in hosts with enteric nervous system dysfunction due to a mutation in the ret locus, which in humans is associated with the intestinal motility disorder known as Hirschsprung disease. In mutant hosts we found reduced gut motility and, confirming our hypothesis, robust coexistence of both bacterial species. This study provides evidence that host-mediated spatial structuring and stochastic perturbation of communities can drive bacterial population dynamics within the gut, and it reveals a new facet of the intestinal host–microbe interface by demonstrating the capacity of the enteric nervous system to influence the microbiota. Ultimately, these findings suggest that therapeutic strategies targeting the intestinal ecosystem should consider the dynamic physical nature of the gut environment.

Probabilistic Invasion Underlies Natural Gut Microbiome Stability

“…While successful invasions are often attributed to fitness and niche differences [25], unsuccessful invasions are additionally attributed to temporal and spatial environmental variation [26] and probabilistic establishment [14, 20, 27]. Thus, the success of an invasion depends upon the invader, the environment, and chance.…”

Integrative Physiology: At the Crossroads of Nutrition, Microbiota, Animal Physiology, and Human Health

“…High-resolution in vivo imaging of gnotobiotic zebrafish colonized with defined communities of fluorescently labeled bacteria has revealed complex behaviors and spatial organization within the intestinal lumen (Jemielita et al, 2014; Rawls et al, 2007; Stephens et al, 2015), and identified host intestinal motility as an important factor governing microbiota composition (Wiles et al, 2016). Initial comparisons of germ-free zebrafish to those colonized with conventional microbiota revealed diverse roles for microbiota on host physiology (Bates et al, 2006; Rawls et al, 2004).…”

Best practices for germ-free derivation and gnotobiotic zebrafish husbandry

“…In some cases, generic bacterial products, such as lipopolysaccharide are sufficient to mediate microbiota effects, whereas in other cases microbial signals are more specific to particular bacterial lineages (Bates et al, 2006; Rawls, Mahowald, Ley, & Gordon, 2006). We have also demonstrated that the host modulates bacterial dynamics and competition within the intestine (Jemielita et al, 2014; Rawls, Mahowald, Goodman, Trent, & Gordon, 2007; Taormina et al, 2012; Wiles et al, 2016) and that gnoto-biotic zebrafish can be used to identify determinants of microbial colonization, including diet (Semova et al, 2012; Stephens et al, 2015; Wong et al, 2015). Gnotobiotic zebrafish have also been used to study colonization resistance against pathogens (Rendueles et al, 2012).…”